Principles of Inheritance and Variation

Core Definitions in Genetics

Inheritance: The process by which characters transfer from parent to progeny.
Genetics: The branch of biology that studies inheritance and the variation of characters from parents to progeny.
Variation: The degree of changes between parents and progeny.
Character and Trait:
- 8Character: A feature of an individual (e.g., seed shape, plant height, eye color).
- Trait: A different variant of a character (e.g., round vs. wrinkled seeds; tall vs. dwarf height; blue vs. brown or black eyes).
Gene and Allele:
- Gene: The unit of inheritance; chemically, it is a segment of DNA. Characters are controlled by genes.
- Allele: Different molecular forms of a gene. According to Mendel, only two molecular forms (alleles) of a gene were possible, but multiple alleles can exist in a population.

Basic Concepts of Chromosomes and Genotype

Homologous Chromosomes: Chromosomes that have the same shape, size, same position of the centromere, and same loci for specific genes.
Chromosome Composition: Includes DNA, RNA, histone proteins, and non-histone proteins (histones and DNA are major components).
Ploidy Levels:
- Haploid ( $n$ ): Single set of chromosomes; only one locus for each gene.
- Diploid ( $2n$ ): Two sets of chromosomes; two loci for each gene.
- Polyploid: More than two sets of chromosomes ( $4n=8$ , etc.).
Dominant and Recessive Alleles:
- Dominant Allele: Expressed in both homozygous and heterozygous conditions; generally represented by capital letters.
- Recessive Allele: Expressed only in the homozygous condition; generally represented by small letters.
Zygosity:
- Homozygous: When both alleles of a gene are of the same type (e.g., $AA, tt$ ).
- Heterozygous: When two different alleles are present (e.g., $Tt, Rr$ ).
- Hemizygous: When only one copy of a gene is present in a diploid organism (e.g., genes on the X-chromosome in males, where recessive alleles express themselves in the absence of a dominant partner).
- Pseudo-dominance: Expression of a recessive allele when its dominant counterpart is missing.
Phenotype and Genotype:
- Phenotype: Observable morphological features of an individual (e.g., tall, dwarf, round).
- Genotype: The genetic complement or makeup of an organism (e.g., $TT, Tt$ ).
- Phenocopy: When two organisms are phenotypically the same due to environmental factors but genotypically different (e.g., a $tt$ dwarf plant becoming tall due to environmental influence, resembling a $TT$ plant).

Mendelian Genetics

Gregor Johann Mendel (1822–1884): Known as the "Father of Genetics." He worked on the garden pea (Pisum sativum) for 7 years (1856–1863). His work was published in 1865 and rediscovered in 1900 by Hugo de Vries, Carl Correns, and Von Tschermak.
Reasons for using Pea Plants: Short life span, bisexual flowers, large number of progeny, and easily visible contrasting traits.
Mendel's Seven Characters in Pea ( $2n=14$ ):
1. Height: Tall (Dominant) vs. Dwarf (Recessive).
2. Seed Shape: Round (D) vs. Wrinkled (R).
3. Seed Color: Yellow (D) vs. Green (R).
4. Pod Shape: Full/Normal (D) vs. Constricted (R).
5. Pod Color: Green (D) vs. Yellow (R).
6. Flower Position: Axial (D) vs. Terminal (R).
7. Flower Color: Violet (D) vs. White (R).

Genetic Crosses and Ratios

Monohybrid Cross: A cross involving one pair of contrasting traits.
- $F_1$ Generation: All offspring show the dominant phenotype ( $Tt$ ).
- $F_2$ Generation (after selfing $F_1$ ):
  - Phenotypic Ratio: $3:1$ (Dominant:Recessive).
  - Genotypic Ratio: $1:2:1$ ( $TT:Tt:tt$ ).
Dihybrid Cross: A cross involving two pairs of contrasting traits (e.g., Round Yellow $RRYY$ x Wrinkled Green $rryy$ ).
- $F_2$ Phenotypic Ratio: $9:3:3:1$ (Round Yellow : Round Green : Wrinkled Yellow : Wrinkled Green).
- $F_2$ Genotypic Ratio: $1:2:1:2:4:2:1:2:1$ .
Back Cross and Test Cross:
- Back Cross: Crossing the offspring with any of its parents.
- Out Cross: Crossing $F_1$ progeny with the homozygous dominant parent to eliminate recessive traits.
- Test Cross: Crossing an individual with a dominant phenotype but unknown genotype with a homozygous recessive parent ( $tt$ or $ww$ ). Outcomes:
  - If all offspring show dominant trait: Parent is homozygous ( $TT$ ).
  - If offspring ratio is $1:1$ : Parent is heterozygous ( $Tt$ ).
Reciprocal Cross: A cross where the sexes of the parents are reversed to see if the trait is sex-linked.
Punnett Square: A graphical representation of all possible genotypes of a genetic cross, developed by Dr. R.C. Punnett.

Mathematical Formulas for Genetics

Number of types of gametes: $2^n$ , where $n$ is the number of heterozygous loci.
Number of types of genotypes: $3^n$ .
Number of types of phenotypes: $2^n$ .
Total zygotic combinations: $\text{Type of male gamete} \times \text{Type of female gamete}$ , or $2^x$ where $x$ is the total number of heterozygous loci in both parents.

Mendel's Laws

Law of Dominance: Characters are controlled by discrete units called factors (genes) which occur in pairs. In a dissimilar pair, one factor dominates the other. This law explains the expression of only one parental trait in $F_1$ . It is not universally accepted due to incomplete dominance and codominance.
Law of Segregation (Purity of Gametes): Two factors of a character segregate during gamete formation so that a gamete carries only one factor. This law is universally accepted.
Law of Independent Assortment: The segregation of one pair of traits is independent of the other pair of traits in a hybrid. Studied in dihybrid crosses. Not universally accepted due to linkage.

Deviations from Mendelian Principles (Gene Interactions)

Intragenic (Allelic) Interaction

Incomplete Dominance: The $F_1$ phenotype is intermediate between dominant and recessive (e.g., Snapdragons or 4 o'clock flowers where Red $RR$ x White $rr$ results in Pink $Rr$ ). Ratio: $1:2:1$ for both phenotype and genotype.
Co-dominance: Both alleles express themselves equally in the $F_1$ generation (e.g., AB blood group, coat color in cattle (Roan), and carrier state in sickle cell anemia ( $Hb^A Hb^S$ )). Ratio: $1:2:1$ .
Multiple Allelism: When more than two alleles of a gene exist in a population (e.g., ABO blood group system involving $I^A, I^B,$ and $i$ alleles, eye color in Drosophila). Number of possible genotypes in a population: $\frac{n(n+1)}{2}$ , where $n$ is the number of alleles.
Pleiotropy: A single gene regulates multiple phenotypic expressions (e.g., Phenylketonuria, starch synthesis and seed shape in peas). In peas, the gene for starch synthesis shows dominance for seed shape (Round vs. Wrinkled) but incomplete dominance for starch grain size (Large, Intermediate, Small).
Lethal Genes: Alleles that cause the death of the organism, usually in the homozygous condition (e.g., coat color in mice, hemophilic gene in females).

Intergenic (Non-allelic) Interaction

Interactions between products of two different genes on the same or different chromosomes that control a single character.
Examples: Epistasis (Dominant $12:3:1$ ; Recessive $9:3:4$ ), Complementary genes ( $9:7$ ), and Duplicate genes ( $15:1$ ).

Quantitative Inheritance (Polygenic Inheritance)

Characters controlled by two or more genes (polygene) where each allele has an additive or cumulative effect.
Environmentally influenced; shows continuous phenotypic expression (bell-shaped curve).
Examples: Human skin color (controlled by 3 pairs of polygenes), human height, kernel color in wheat (2 pairs).
Formulas for Polygenic Inheritance:
- Number of Phenotypes: $2n + 1$ , where $n$ is the number of pairs of polygenes.
- Number of Genotypes: $3^n$ .

Chromosomal Theory of Inheritance

Proposed by Sutton and Boveri (1902). They stated that chromosomes are the vehicles of heredity and their behavior parallels the behavior of Mendelian factors (genes).
Experimental verification provided by Thomas Hunt Morgan using Drosophila melanogaster (fruit fly).
Why Drosophila? Short life cycle (2 weeks), easy culture, many progeny, only 4 pairs of chromosomes, distinct male/female morphology.

Linkage and Recombination

Linkage: The physical association of genes on the same chromosome. Term coined by T.H. Morgan.
Recombination: The production of non-parental gene combinations due to crossing over.
Strength of Linkage: Inversely proportional to the distance between genes ( $\text{Linkage} \propto \frac{1}{\text{Distance}}$ ).
Linkage Group: The set of genes on a single chromosome that tend to be inherited together. The number of linkage groups equals the haploid number ( $n$ ) of chromosomes (e.g., Human female: 23; Human male: 24; Pea: 7; Drosophila male: 5).
Genetic Mapping: Alfred Sturtevant used recombination frequency to determine the distance between genes. Unit: centiMorgan (cM) or map unit.
- $\text{Recombination Frequency (RF)} = \frac{\text{Number of Recombinants}}{\text{Total Progeny}} \times 100$ .
- $1\% \text{ RF} = 1 \text{ cM}$ .

Sex Determination

Chromosomal Basis:
- Male Heterogamety: Male produces two types of gametes.
  - XX-XO type: Grasshoppers (Male is $XO$ , Female is $XX$ ).
  - XX-XY type: Humans, Drosophila (Male is $XY$ , Female is $XX$ ).
- Female Heterogamety: Female produces two types of gametes.
  - ZZ-ZW type: Birds (Female is $ZW$ , Male is $ZZ$ ).
  - ZZ-ZO type: Moths, Butterflies (Female is $ZO$ , Male is $ZZ$ ).
Sex Determination in Honey Bees: Haplodiploid system. Males (drones) are haploid ( $n=16$ ) and develop via parthenogenesis. Females (Queens/Workers) are diploid ( $2n=32$ ) and develop from fertilized eggs. Drones have no father or sons but have grandfathers and grandsons.
Barr Body: Deactivated X-chromosomes in females. Number of Barr bodies = Total X chromosomes - 1.

Scientific Traits Classification

Sex-linked traits: Controlled by genes on sex chromosomes (e.g., Hemophilia, Colorblindness).
Sex-limited traits: Autosomal genes expressed in only one sex (e.g., Milk glands in females, beard in males).
Sex-influenced traits: Autosomal genes where dominance varies by sex (e.g., Pattern baldness in males).
Criss-cross Inheritance: Father transfers trait to grandson through daughter; mother transfers to granddaughter through son.

Mutation

Definitions: Sudden, random, discontinuous changes in genotype and phenotype.
Gene Mutation: Change in DNA sequence.
- Point Mutation: Change in a single base pair (e.g., Sickle cell anemia).
- Frame-shift Mutation: Insertion or deletion of nucleotides not in multiples of 3.
- Substitution: One nucleotide replaced by another (Transition: Purine-Purine/Pyrimidine-Pyrimidine; Transversion: Purine-Pyrimidine).
Chromosomal Mutation: Change in structure (aberration) or number (genomic mutation).
- Aneuploidy: Changes not in multiples of the basic set (e.g., Monosomy ( $2n-1$ ), Trisomy ( $2n+1$ ), Nullisomy ( $2n-2$ )).
- Euploidy: Changes in sets of chromosomes (Haploidy, Polyploidy).
Mutagens: Agents that induce mutation (Physical: X-rays, UV rays; Chemical: Mustard gas).

Genetic Disorders

Mendelian Disorders (Gene-related)

Hemophilia: X-linked recessive. Blood fails to clot. Queen Victoria was a carrier.
Colorblindness: X-linked recessive. Inability to distinguish red and green. More common in males ( $8\%$ ) than females ( $0.4\%$ ).
Sickle Cell Anemia: Autosomal recessive. Point mutation at the 6th position of the $\beta$ -globin chain where Glutamic acid is replaced by Valine ( $GAG \rightarrow GUG$ ). RBCs become sickle-shaped under low oxygen.
Phenylketonuria (PKU): Autosomal recessive. Lack of phenylalanine hydroxylase enzyme leading to accumulation of phenylalanine, causing mental retardation and de-pigmentation.
Thalassemia: Autosomal recessive. Quantitative disorder with reduced synthesis of $\alpha$ or $\beta$ globin chains.

Chromosomal Disorders

Down Syndrome: Trisomy of chromosome 21 ( $2n+1$ ). Characteristics: short stature, furrowed tongue, mental retardation.
Turner's Syndrome: Monosomy of X chromosome in females ( $44+XO$ ). Sterile females with underdeveloped feminine characters.
Klinefelter's Syndrome: Trisomy ( $44+XXY$ ) in males. Sterile males with feminine features like Gynaecomastia.

Pedigree Analysis Symbols

Square: Male.
Circle: Female.
Diamond: Sex unspecified.
Filled symbol: Affected individual.
Horizontal line between symbols: Marriage/Mating.
Vertical line down: Offspring.
Circle inside a circle: Carrier (sex-linked).
Double horizontal line: Consanguineous mating (between relatives).

Cytoplasmic Inheritance

Inheritance controlled by mitochondrial or chloroplast genes.
Traits are transferred from the mother to all progeny (maternal inheritance) because the egg provides more cytoplasm than the sperm.